Quaternary ammonium salts of n-substituted palmitamides

ABSTRACT

A number of new quaternary ammonium salts of n-substituted palmitamides have been prepared by conventional methods. These derivatives have been characterized by exhibiting antimycotic activity and three of the derivatives, 4-palmitoyl-1,1dimethylpiperazinium iodide, (2palmitoylaminoethyl)trimethylammonium iodide, and 4-palmitoyl-1methyl-1-(1,4,5,6,7,7-hexachlorobicyclo(2.2.1)-hepta-2,5-diene -2methylene)piperazinium bromide have been further characterized by exhibiting nematocidal activity.

United States Patent [1 1 Mod et al.

1 QUATERNARY AMMONIUM SALTS OF N-SUBSTITUTED PALMITAMIDES [75]Inventors: Robert R. Mod; Frank C. Magne;

Evald L. Skau; Gene Sumrell, all of New Orleans, La. 1

[73} Assignee: The United States of America as represented by theSecretary of Agriculture, Washington, DC.

22 Filed: June 23,1972

211 Appl. N0.: 265,869

[52] US. Cl..... 260/404.5, 260/268 BC, 260/268 C, 260/293.88, 424/30,424/250, 424/267 [51] Int. Cl. C07c 103/30 [58] Field of Search 260/4045[56] References Cited UNITED STATES PATENTS 1.737.458 1 [/1929 Hartmannet a1 260/4045 2.303.191 11/1942 Baldwin et a1 .1 260/4045 2.589.6743/1952 Cook ct all 260/4045 OTHER PUBLICATIONS Muzyczko et a1,J,A.O.C.S., Vol. 45111), 1968, pp.

[ 1 Mar. 4, 1975 Chem. Abstracts, Vol. 58, 11375(b) 1l375(b).

Chem. Abstracts, Vol. 62, 9002(c) Primary Examiner-Lewis Gotts Assistantliruminer-Ethel G. Love Attorney, Agent, or Finn-M. Howard Silverstein;Max D. Hensley [57] ABSTRACT 3 Claims, N0 Drawings 1 2 QUATERNARYAMMONIUM SALTS ()F r 4-palmitoyl-l,l-dime-thylpiperazinium iodide.

N-SUBSTITUTED PALMITAMIDES A non-exclusive, irrevocable, royalty-freelicense in [CH (131 no N M (CH I the invention herein described,throughout the world for all purposes of the United States Government,with 5 the power to grant sublicenses for such purposes, is herebygranted to the Government of the United States M f Amencu tcn am no u N(m I This invention relates to certain new nitrogen con- 7 taiht'hgcompouhds- More Particularly this invention to4-stearoyl-l,1-dimethylpiperazinium iodide. relates to quaternaryammonium salts of tertiary amino 4-decanoyl-l,l-dimethylpiperaziniumiodide.

aliphatic amides which exhibit antimicrobial and ,nematocidal activity.The quaternary ammonium salts that to N 9 1 l are the subject of thisinvention are characterized by the fact that as growth inhibitors y areettecttve (2-decanoylaminoethyl)trimethylammonium iodide,

against a variety of microorganisms that includebacte- [CH3(CH2)8CONHCH2CH2N CH3)3]+1 Th1 and molds of which are Pathogenic-t some of(2-palmitoylaminoethyl)trimethylammonium iodide,

these derivatives are further characterized by their ne- [CHACH MCONHCHCH MCH +1 matocidal activity against Panagrellus redivii'us. 2O (2 1 i 1i h |)di h l h l i The findings herein disclosed are consideredremarkiodide, [C -M UH fiHzWCQI-ls)2 able in that in some notableinstances compounds that CH 1 are closely related from the pointof viewof chemical (2-oleoylaminoethyl)trimethylammonium iodide,

architecture exhibit quite opposite effects against the CH (CH CH:CH(CHCONHCH CH N(CH;,);,

same organisms. For example. one compound may ex-' 25 1 1" hibitproperties as a growth inhibitor against one parti- .dimethiodide of 9(lO)-[( lcluar organism while a closely related counterpart maymethylpiperazino)carbonyl]-4--0ctadecanoyl-lserve to promote increasedgrowth for the same organmethylpiperazine,

ism. Some of these amides exhibit broad antimicrobial m spectrum,whereas others exhibit selective antimicro- 30 bidl Spectrum CH(CH co ur: (m 2| The compounds which are the subject of this inven- H tion are:My 15 (2-stearoylaminoethyl)trimethyl ammonium iodide, x I

l HM 2)m z 2 a)3l 35 I (Z-palmitoylaminoethyl)diethylpropargylammoniuml,4-xylylene-bis (4-oleoyl-l-methylpiperazinium lTl'UlilitlC, chloride),

CH CH -H- enigma on CH C =CH] Br' l,4-xylylene-bis(4palmitoyl-l-methylpiperazinium 4-palmitoyl-l-methyl-l-[ l,4,5,6,7,7-chloride),

i m I" 1-1, H fin tcn mcou nsn o N M M J zcihexachlorobicyclo[2.2.1]-hepta-2.5-diene'2- methyleneIpiperazinlambromide.

CH (CH C0 n ntcn cu /l. fil

cl-c -cc1 --c ct 3,869,483 3 44-Palmitoyl-l-methyl-l-pr0pargylpiperazinium bro-- mide,

I c=o tcu (ca co NUMCHB) cn c-cul Br LII NHCH CH N (C H CH4-oleoyl-l-methyl-l-propargylpiperazinium bromide,

A (2-stearoylaminoethyl)diethylmethylammonium io- [fl (CH CH:CH(CH C NMCH C11 6: f l fi 3( 2)IG 2 2 2 5)2 :ti'

. 2-(oleoylaminoethyl)pro ar 'ldimeth 'lammonium4-oleoyl-l,l-dimethylpiperazlnium iodide, bromide,[CH3(CH2)7EH:g.H(CH2iCONHCHi:

H N(CH,-,) CH C CH] Br [CH (CN CN:CH(CH CO N N(CH I' I5(Z-palmitoylaminoethyl)propargyldimethylammonium bromide.

i fl( 2)l-l 2 2 5l)2 CH C' CHFBr andN-methyl-N-(2-oleoylaminoethyl)piperidinium [CH3 7CN:CH 2)7 l BI IlOdlde 4-oleoyll l -dimethylpiperazinium bromide,

4-oleoyl-l-methyl-l-ethylpiperazinium bromide, H:CH(CH CONHCH CH N l' 32 7 2 7 2 2 l' CH CH C H 3 [cu (cn cu cu(cu co N u 2 Br 25.

4-palmitoyl-l,l-dimethylpiperazinium bromide, The newnitrogen-containing compounds which are the subject of this inventionwere prepared by conventional methods.

The bioactivity of these various new nitrogenv containing compounds hasbeen established by us in 4-palmitoyl-l-methyl-l-benzylpiperaziniumchloride, vitro but, as will be apparent to those skilled in the artspertaining to the growth inhibition of bacteria and co K (CH c" 6 molds,thecompounds, besides being used as such, will 3 2 I 3 2 5 forutilitarian purposes commonly be formulated using a diluent that can beeither liquid, viscous, or solid.

p,p-oxybis(4-palmitoyl-l-methyl-l- A wide variety of extending agents isoperable, the benzylpiperazinium chloride), only significant requirementbeing that the diluent or r'"\ I r- [CH (ca mcon, ,l l(CH )CCH (CH )N 0CEH 4-palmitoyl-l,l-dimethylpiperazinium methyl sulextender be inert withrespect to the amide involved.

fate, Petroleum jellies, various alcohols and polyois, vegetable oilsand the like are suitable. m

Specific examples showing the preparation of each of 3 (cflfilhco N(W921 W350l the new compounds being claimed are set forth below alongwith appropriate data in tabular form which is4-oleoyl-l,l-dimethylpiperazinium methyl sulfate. being submitted forthe purpose of establishing the growth inhibiting properties of theclaimed com- EXPERIMENTAL p,p-xylylenebisl(Z-palmitoylaminoethyl)diethylam- Difco Bacto Dehydrated StockCulture Agar at pH monium chloride]. 7.0, and Difco DehydratedMycological Agar at pH 7.0 [CH;;(CH CONHCH CH N(C H5) CH C H C- wereselected to test the inhibition of the bacteria and H- ,N(C H5) CH CHNHCO (CH CH 2Cl ,0 mold cultures, respectively.N,N-but-2-enylenebis(4-oleoyl-l- Fatty acid derivatives were screenedfor their antimimethylpiperazinium chloride), crobial activity againsttwo bacteria Bacillus Species and Pseudomonas Species; five molds mostoflwhich are pathogenic Candida a/hicans, Micrm'porum gypscum,Triclmp/rvmn rubrum, Tric/mp/rrlon riu/aceum,

and Aspergillusjlm'us, as illustrated in Table l. dimethiodide of 9(l())-[(2- Several fatty acid derivatives were screened for theirdiethylaminoethyllcarbonyll-N-(l-d clhy minoenematocidal activityagainst Iunugrvl/us Rl't/ll'illlS as thyl)octadecanamide, shown in TableII.

pounds were introduced into the stainless steel cylin ders.

Streaked and poured agar plates were used to measure the antimycoticactivity against molds. The

streaked agar plates were prepared by streaking the hardened agar plateswith the test mold, and the poured agar plates were prepared by pouringdilutions of mold spores over the hardened agar plates. The compoundswere then added onto specified areas of these streaked.

and poured agar plates. The paper disc method was used to evaluate theliquid and solid compounds, the solid compounds were simply dissolved inglycerol or ethanol before applying onto the paper disc. The solidcompounds were also tested in pure form by introducing the solidmaterial directly on the surface of the inocul'ated agar plates.

To eliminate any error which could result from an insufficient number oftests, a minimum of three experiments employing duplicate plates wereused for measurig the antimicrobial activity of each compound.

All test plates were incubated at the optimum growing temperature foreach organism. The tabulated results illustrated in Table l wereobtained from periodic readings after 1,2,3, and 5 days, respectively.

The compounds tested as nematocides were made up to 100,000 p.p.m. inorganic solvent; in most cases, acetone was employed. This solution wasdiluted 1:10 in water with 1 percent Tween 80. The 10,000 p.p.m.solution was added to an equal volume of nematocides, Panagrellusredivivus in water to give a final concentration of 5000 p.p.m. After 24hours, the organisms were examined under the microscope and the numberof dead nematodes ascertained.

EXAMPLE 1 (2-Palmitoylaminoethyl)trimetbyl ammonium iodide.

Ten grams (0.031 mole) of N-(dimethylaminoethy1)- palmitamide wasdissolved in 25 ml of diethylether, after which 4.4 grams (0.031 mole)of methyl iodide was added. After standing for ten hours, the mixturewas centrifuged employing a Skau tube. The whitesolid was given tworecrystallizations from a 1:1 acetoneethanol mixture. The product,(2-palmitoylaminoethyl)trimethyl ammonium iodide had a nitrogen contentof 5.9% (theory 6.17%).

EXAMPLE 2 4-Palmitoyll -methyl-1-[ I ,4,5,6,7,7- hexachlorobicyclo[2.2.l]hepta-2,S-diene-Z-methylene]pipera2inium bromide.

A sample of 11.6 grams (0.030 mole) of l,4,5,6,7,7-hexachloro-Z-bromomethylbicyclol2.2.1]-2,5- heptadiene; grams (0.030mole) of N-palmitoyl-N'- methylpiperazine and 50 ml of2,2-dimethoxypropane were placed in a flask equipped with refluxcondenser. The mixture was refluxed for 10 hours after which the solventwas removed by stripping under reduced pressure. The product was givenfour recrystallizations from 1:1 acetone-ethanol mixture and dried overP 0 in a vacuum dessicator. The product, 4-Palmitoyl-1 -methyl-1-[ l,4,5,6,7,7-hexachlorobicyclo[2.2. l ]hepta-2,5-diene-2-methylenelpiperazinium bromide had a nitrogen content of3.90% (theory 3.84%).

EXAMPLE 3 (2-Stearoylan 1inoethyl)trimethyl ammonium iodide.

This compound was prepared by the procedure of Example 1, from 5 grams(0.015 mole) of N- (dimethylaminoethyl)stearamide and 2.1 grams (0.015mole) of methyl iodide. The product, (2- Stearoylaminoethyl)trimethylammonium iodide, had a nitrogen content of 5.31% (theory 5.81%).

EXAMPLE 4 (Z-Decanoylaminoethyl)trimethyl ammonium iodide.

This compound was prepared by the procedure of Example 1, from 10 grams(0.042 mole) of N- (dimethylaminoethyl)decanamide and 5.9 grams (0.042mole) of methyl iodide. The product, (2- Decanoylaminoethy1)trimethylammonium iodide, had a nitrogen content of 7.14% theory 7.57%).

EXAMPLE 5 (2-Oleoylaminoethyl)trimethyl ammonium iodide.

This compound was prepared by the procedure of Example 1, from 5 grams(0.015 mole) of N- (Dimethylaminoethyl)oleamide and 2 grams (0.014 mole)of methyl iodide. The product, (2-Oleoylamino' ethyl)trimethyl ammoniumiodide, had a nitrogen content of 5.71% (theory 5.83%).

EXAMPLE 6 (2-Palmitoylaminoethyl)diethylmethyl ammonium iodide. Thiscompound was prepared by the procedure of Example 1, from 10 grams(0.028 mole) of N- (Diethylaminoethyl) palmitamide and 4 grams (0.028mole) of methyl iodide. The product, (2-Palmitoylaminoethyl)diethylmethylammonium iodide, had a nitrogen contentof 5.27% (theory 5.64%).

EXAMPLE 7 (Z-Palmitoylaminciethyl)diethylpropargylammonium bromide.

This compound was prepared by the procedure of Example 1, from 3 grams(0.008 mole) of N (Diethylaminoethyl)palmitamide and 1 grams (0.008

mole) of propargyl bromide. The product, (2-

Palmitoylaminoethyl)diethylpropargylammonium bromide, had a nitrogencontent of5.89% (theory 5.92%).

EXAMPLE 8 EXAMPLE 9 4-Stearoyl-l,l-dimethylpiperaziniu-m iodide.

This compound was prepared by the procedure of Example 1, from 10 grams(0.027 mole) of N-stearoyl- N'-methylpiperazine and 3.9 grams (0.028mole) of methyl iodide. The product, 4-stearoyl-l,ldimethylpiperaziniumiodide, had a. nitrogen content of 5.46% (theory 5.51%).

EXAMPLE ll 4-Decanoyl-l,l-dimethylpiperazinium iodide.

This compound was prepared by the procedure of Example 1, from 10 grams(0.039 mole) of N- Decanoyl-N-methylpiperazine and 5.6 grams (0.039mole) of methyl iodide. The product, 4-decanoyl-l,ldimethylpiperaziniumiodide, had a nitrogen content of 7.02% (theory 7.08%).

EXAMPLE l2 4-Palmitoyll -methyl-l -propargylpiperazinium mide.

This compound was prepared by the procedure of Example 1 from 10 grams(0.030 mole) of N-palmitoyl- N-methylpiperazine and 3.8 grams (0.032mole) of propargyl bromide. The product,4-Palmitoyl-lmethyl-1-propargylpiperazinium bromide, had a nitrogencontent of 5.99% (theory 6.12%).

EXAMPLE l3 4-Oleoyl- 1 -methyl- 1 -propargylpiperazinium bromide.

This compound was prepared by the procedure of Example 1 from 10 grams(0.027 mole) of N-oleoyl-N-methyl-piperazine and 3.5 grams (0.029 mole)of propargyl bromide. The product,4-Oleoyl-lmethyl-l-propargylpiperazinium bromide, had a nitrogen contentof 5.73% (theory 5.79%).

EXAMPLE l4 4-Oleoyl-l,l-dimethylpiperazinium iodide.

This compound was prepared by the procedure of Example 1, from 10 grams(0.027 mole) of N-oleoyl-N-methylpiperazine and 4.5 grams (0.032 mole)of methyl iodide. The product, 4-Oleoyl-l,1- dimethylpiperaziniumiodide, had a nitrogen content of 5.52% (theory 5.54%).

EXAMPLE l5 4-Oleoyl-l-methyl-l-ethylpiperazinium bromide.

This compound was prepared by the procedure of Example 1, from 10 grams(0.027 mole) of N-Oleoyl-N-methylpiperazine and 4 grams (0.036

bro-

"mole) of ethyl bromide. The product, 4-Oleoyl-1-methyl-l-ethylpiperazinium bromide, had a nitrogen content of 5.86%(theory 5.92%).

EXAMPLE l6 4-Oleoyl-l ,l-dimethylpiperazinium bromide.

This compound was prepared by the procedure of Example 1, from 5 grams(0.013 mole) of N-Oleoyl-N'-methylpiperazine and 1.4 grams (0.015 mole)of methyl bromide. The product, 4-Oleoy|-l,ldimethylpiperaziniumbromide, had a nitrogen content of 5.50% (theory 6.10%).

EXAMPLE 17 4-Palmitoyl-l,l-dimethylpiperazinium bromide.

This compound was prepared by the procedure of Fimmnlp l f'rnm 8 cram:(ll mole) nf N-nnlmitnvl- 8 N'-methylpiperazine and 1.7 grams (0.018mole) of methyl bromide. The product,4-Palmitoyl-1,ldimethylpiperazinium bromide, had a nitrogen content of6.18% (theory 6.46

EXAMPLE l8 4-Palmitoyl-l-methyl-l-benzylpiperazinium chloride.

This compound was prepared by the procedure of Example 1, from 10 grams(0.030 mole) of N- palmitoyl-N'-methylpiperazine and 4 grams (0.032mole) of benzyl chloride. The product,4-Palmitoyl-lmethyl-l-benzylpiperazinium chloride, had a nitrogencontent of 5.85% (theory 6.02%).

EXAMPLE l9 1,4-Xylylene-bis(4-oleoyl-l-methylpiperazinium chloride).

This compound was prepared by the procedure of Example 1, from. 10 grams(0.027 mole) of N-Oleoyl-N-methylpiperazine and 2.4 grams (0.013

mole) of a,a-dichloro-p-xylene. The product, 1,4-'

Xylylene-bis(4-oleoyl-1-methylpiperazinium chloride), had a nitrogencontent of 5.54% (theory 6.20%).

EXAMPLE 20 l,4-Xylylene-bis(4-palmitoyl- 1 -methylpiperaziniumchloride).

This compound was prepared by the procedure of Example 1, from 10 grams(0.030 mole) of N- Palmitoyl-N-methylpiperazine and 2.6 grams (0.015mole) of a,a-dichloro-p-xylene. The product, 1,4-Xylylene-bis(4-palmitoyl-l-methylpiperazinium chloride), had a nitrogencontent of 6.69% (theory 6.58%).

EXAMPLE 21 N,N'-But-2-enylenebis(4-oleoyl-1-methylpiperaziniumchloride).

This compound was prepared by the procedure of Example 1, from 10 grams(0.027 mole) of N-Oleoyl-N-methylpiperazine and 1.7 grams (0.013 mole)of 1,4-dichloro-2-butene. The product, N,N-But-2-enylene-bis(4-oleoyl-1-methylpiperazinium chloride), had anitrogen content of 6.15% (theory 6.56%).

EXAMPLE 22 4-Palmitoyl-l,l-dimethylpiperazinium methyl sulfate.

This compound was prepared by the procedure of Example 1, from 10 grams(0.030 mole) of N- Palmitoyl-N'-methylpiperazine and 4 grams (0.032

'mole of dimethyl sulfate. The product, 4-Palmitoyl-l ,l-

dimethylpiperazinium methyl sulfate, had a nitrogen content of 5.95%(theory 6.03%).

EXAMPLE 23 4-Oleoyl-1,l-dimethylpiperazinium methyl sulfate.

This compound was prepared by the procedure of Example 1, from 9 grams(0.025 mole) of N-Oleoyl-N-methylpiperazine and 4 grams (0.032 mole) ofdimethyl sulfate. The product, 4-Oleoyl-l ,ldimethylpiperazinium methylsulfate, had a nitrogen content of 5.61% (theory 5.71%).

EXAMPLE 24 p,p'-Oxybis( 4-palmit0yll-methyll benzylpiperaziniumchloride).

This compound was prepared by the procedure of Fvnmnlq l Pram i nrnmnIfl fili mn]n\ n4 kl nnlmhnnl Dimethiodide N-methylpiperazine and 2grams (0.008 mole) of a,a-dichloroditoluoyl ether. The product, p,p'-oxybis(4-palmitoyl-1-methyl-l-benzylpiperazinium chloride), had anitrogen content of 5.57% (theory 5.93%).

EXAMPLE 25 of 9(10)-[(1-methylpiperazino)carbonyl]-4-octadecanoyl-l-methylpiperazine.

This compound was prepared by the procedure of Example 1, from 5 grams(0.01 mole) of 9(10)-[lmethylpiperazino)carbonyl]-4-octadecanoy1-l-methylpiperazine and3 grams (0.021 mole) of methyl iodide. The product, dimethiodide of9(10)-[(lmethylpiperazino)carbonyl]-4-octadecanoyl-l-methylpiperazine,had a nitrogen content of 6.93% (theory 7.21%).

EXAMPLE 26 N-Methyl-N-(2-oleoylaminoethy1)piperidinium iodide.

This compound was prepared by the procedure of Example 1, from 5 grams(0.013 mole) of N-(2-Piperidinoethy1)oleamide and 1.8 grams (0.013 mole)of methyl iodide. The product, N-methyl-N-(Z-oleoylaminoethyl)piperidinium iodide, had a nitrogen content of 5.06%(theory 5.24%).

"EXAMPLE 27 (2-Palmitoy1aminoethyl)propargyldimethylammonium bromide.

This compound was prepared by the procedure of Example 1, from 12 grams(0.036 mole) of N- (dimethylaminoethyl)palmitamide and 4.4 grams (0.036mole) of propargyl bromide. The product, (2-

Palmitoylam inoethyl )propargyldimethylammonium bromide, had a nitrogencontent of 6.10% (theory EXAMPLE 28(2-Oleoylaminoethyl)propargyldimethylammonium bromide.

This compound was prepared by the procedure of Example 1, from 5 grams(0.014 mole) of N- (dimethylaminoethyl)oleamide and 1.7 grams (0.014mole) of propargyl bromide. The product, (2-oleoylaminoethyl)propargyldimethylammonium bromide, had a nitrogencontent of5.77% (theory 5.94%).

EXAM PLE 2.9

EXAMPLE 30 (Z-Stearoylaminoethyl)diethylmethylammonium dide.

This compound was prepared by the procedure of Example 1. from 5 grams(0.013 mole) of N- (Diethylaminoethyl)stearamide and 1.9 grams (0.013mole) of methyl iodide. The product, (2-Stearoylaminoethyl)diethylmethylammonium iodide,

had anitrogen content of 5 .05% theory 5.l 1%).

TABLE I ANTIMICROBIAL ACTIVITY OF SOME FATTY ACID DERIVATIVES CompoundsAntimicrobial Activity" Microorganisms A B C D E F G(2-Stearoylaminoethyl )trimethyl ammonion iodide x x x x x(2-Palmitoylaminoethyl)diethylproparylammonium bromide 4-PaImitoyl-l-methyl- 1 [1.4,5,6,7,7-hexachlorobicyclo[2.2.l ]hepta-2,5-

diene-Z-methylenelpiperazinium bromide 4-Palmitoyl-l,l-dimethylpiperazinium iodide XX X XX XX 4-Decanoyl-l,I-dimethylpiperazinium iodide XX XX XX XX XX XX 4-Stearoyll 1-dimethylpiperazinium iodide (Z-Decanoylaminoethyl)trimethyl ammoniumiodide.

XX XX (Z-Palmitoylaminoethyl)tri methyl ammonium iodide x x x x XX X(Z-Palmitoylaminoethyl)diethylmethyl ammonium iodide XX XX(2-Oleoylaminocthyl )trimethyl ammonium iodide Dimethiodide of 91 l0)-l(lmethyl ipcruzino)carbonyll- 4-octa ecanoyl-I-methylpiperazine xx xx xxxx xx 1,4-Xylylene-bis(4-oleoyl-1- methylpiperazinium chloride) x,4-Xylylene-bis(4-palmitoyl-1- me thylpiperazinium chloride) 7ANTIMICROBIAL ACTIVITY OF SOME FATTY ACID DERIVATIVES AntimicrobialActivity" Microorganisms Comgounds A B C D E F G 4'Palmitoyl- 1 -methyl-I propargylpiperazinium bromide 4+ xx x xx 4-Olcoyl- I methyl-l-Kmpargylpipcrazinium mmide x xx xx 4-Olcoyl- I I -dimcthylpiperaziniumiodide x xx +1- 4 Oleoyl l ,l -dimethylpiperazinium bromide xx xx xx ll-4-Oleoyl-1-methyl-l-ethylpipcrazinium bromide xx xx x 4-Palmitoyl-l l-dimethylpiperazinium bromide xx xx xx 4-Palmitoyl- 1 -methyl- 1-benzylpiperazinium chloride xx xxp,p'-Oxybis(4-palmitoyl-lmethyl-1-benzylpiperazinium chloride) x x x4-Palmitoyl-l ,l -dimethylpiper' azinium methyl sulfate -H- xx xx xx4-OIeoyl-l ,l-dimethylpiperazinium methyl sulfate xx xx xx xxp.p-Xylylene bis(2-palmitoylaminoethyldiethyh ammonium chloride) +1- xxx N,N'-But-2-enylenebis(4-oleoyll-methylpiperazinium chloride)Dimethiodide of 9( l)[(2-diethylaminoethyl)carbonyH-N-(2-diethylaminoethyl)octa decanamide -H- x(2-Stearoylaminoethyl)diethylmethylammonium iodide xx xx xx xx(2-Oleoylaminoethyl)propargyldimethylammonium bromide xx xx xx -H-(2-Palmitoylaminoethyl)propargyldimethylammonium bromide xx xx xx xxN-Methyl-N-(2-Ole0ylaminoethyl)piperidinium iodide llxx xx l/ -H- Thezone of inhibition was at least 0.5 cm

beyond disc or cylinder area at 120 hrs. The zone of inhibition was lessthan 0.5 cm

beyond disc or cylinder area at 120 hrs. xx Organisms failed to grow ondisc or cylinder area at 120 hrs. x Slight growth on the saturated discor cylinder area at 120 hrs. No inhibition detectable. 2/ A=Trichophytonrubrum B=Microsporum gypseum C=Aspergillus flavus D=Trichophylonviolaceum E=Candidu albicans F=Pseud0m0nas Sp. G=Bacillus Sp. H A V V WTABLE II NEMATOCIDAL EVALUATION OF FATTY AMIDE DERIVATIVES Organism Comound Panagrellus Redivivus Cone.

ppm Dead Affected Normal 4-Palmitoyl-l 1 -dimethyl-piperazinium 10 ,000100 0 0 iodide 1,000 100 0 0 100 90 10 0 75 80 0 50 20 25 0 20 10 0 10(2-Palmitoylaminoethyhtrimethyl 10,000 100 0 0 ammonium iodide 1,000 1000 0 100 5 0 75 80 15 5 5.9 v W ,5!) 4Q 10 TABLE II Continued NEMATOCIDALEVALUATION OF FATTY AMIDE DERIVATIVES Organism Compound PanagrellusRedivivus Conc.

ppm Dead Affected Norma] 4-Palmitoyl-l-methyl-l-(l,4,5.6,7,7- 10,000 1000 0 hexachlorobicyclo[2.2. l]-hepta-2,5- 1,000 100 0 0diene-2methylene)piperazinium bromide 100 60 20 75 20 50 50 5 10 85 25 010 90 10 0 0 100 w l i 7" 2.(2-0leoylaminoethyl)propargyldimethylammonium bromide.

3. (2- almito laminoeth l dIe th 1 to a l l.(2-palmftoylarninoethyl)propargyldlmethylam- 2O moniunq bmnqide. y y) ypp rgy'am monium bromide. In

1. (2-PALMITOYLAMINOETHYL)PROPARGYLDIMETHYLAMMONIUM BROMIDE. 2.(2-oleoylaminoethyl)propargyldimethylammonium bromide. 3.(2-palmitoylaminoethyl)diethylpropargylammonium bromide.